Abstract:
:Triple-negative breast cancer (TNBC) cells are modulated in reaction to tumor-infiltrating lymphocytes. However, their specific responses to this immune pressure are unknown. In order to address this question, we first used mRNA sequencing to compare the immunophenotype of the TNBC cell line MDA-MB-231 and the luminal breast cancer cell line MCF7 after both were cocultured with activated human T cells. Despite similarities in the cytokine-induced immune signatures of the two cell lines, MDA-MD-231 cells were able to transcribe more IDO1 than MCF7 cells. The two cell lines had similar upstream JAK/STAT1 signaling and IDO1 mRNA stability. However, using a series of breast cancer cell lines, IFNγ stimulated IDO1 protein expression and enzymatic activity only in ER-, not ER+, cell lines. Treatment with 5-aza-deoxycytidine reversed the suppression of IDO1 expression in MCF7 cells, suggesting that DNA methylation was potentially involved in IDO1 induction. By analyzing several breast cancer datasets, we discovered subtype-specific mRNA and promoter methylation differences in IDO1, with TNBC/basal subtypes exhibiting lower methylation/higher expression and ER+/luminal subtypes exhibiting higher methylation/lower expression. We confirmed this trend of IDO1 methylation by bisulfite pyrosequencing breast cancer cell lines and an independent cohort of primary breast tumors. Taken together, these findings suggest that IDO1 promoter methylation regulates anti-immune responses in breast cancer subtypes and could be used as a predictive biomarker for IDO1 inhibitor-based immunotherapy. Cancer Immunol Res; 5(4); 330-44. ©2017 AACR.
journal_name
Cancer Immunol Resjournal_title
Cancer immunology researchauthors
Noonepalle SK,Gu F,Lee EJ,Choi JH,Han Q,Kim J,Ouzounova M,Shull AY,Pei L,Hsu PY,Kolhe R,Shi F,Choi J,Chiou K,Huang TH,Korkaya H,Deng L,Xin HB,Huang S,Thangaraju M,Sreekumar A,Ambs S,Tang SC,Munn DH,Shi Hdoi
10.1158/2326-6066.CIR-16-0182subject
Has Abstractpub_date
2017-04-01 00:00:00pages
330-344issue
4eissn
2326-6066issn
2326-6074pii
2326-6066.CIR-16-0182journal_volume
5pub_type
杂志文章abstract::We assessed the contribution of IL1 signaling molecules to malignant tumor growth using IL1β-/-, IL1α-/-, and IL1R1-/- mice. Tumors grew progressively in IL1R-/- and IL1α-/- mice but were often absent in IL1β-/- mice. This was observed whether tumors were implanted intradermally or injected intravenously and was true ...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-19-0552
更新日期:2020-05-01 00:00:00
abstract::Programmed death 1 (PD-1) and PD ligand 1 (PD-L1) inhibitors have shown activity in metastatic clear cell renal cell carcinoma (ccRCC). Data on the activity of these agents in patients with non-clear cell RCC (nccRCC) or patients with sarcomatoid/rhabdoid differentiation are limited. In this multicenter analysis, we e...
journal_title:Cancer immunology research
pub_type: 杂志文章,多中心研究
doi:10.1158/2326-6066.CIR-17-0475
更新日期:2018-07-01 00:00:00
abstract::Chimeric antigen receptor (CAR) T-cell therapy has shown remarkable successes in fighting B-cell leukemias/lymphomas. Promising response rates are reported in patients treated with B-cell maturation antigen (BCMA) CAR T cells for multiple myeloma. However, responses appear to be nondurable, highlighting the need to ex...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-20-0118
更新日期:2020-12-01 00:00:00
abstract::The importance of natural killer (NK) cells in the early immune response to viral or bacterial infection is well known. However, the phenotype, function, and physiologic role of NK cells during the late stage of persistent viral infection have not been extensively studied. Here, we characterized NK cells in mice persi...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-18-0403
更新日期:2019-04-01 00:00:00
abstract::Natural killer (NK) cells contribute to clinical responses in patients treated with rituximab, but the rules determining NK-cell responsiveness to mAb therapies are poorly defined. A deeper understanding of the mechanisms responsible for antibody-dependent cellular cytotoxicity (ADCC) could yield useful biomarkers for...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-13-0158
更新日期:2014-09-01 00:00:00
abstract::Hypoxia-driven, A2A adenosine receptor (A2AR)-mediated (hypoxia-A2-adenosinergic), T-cell-autonomous immunosuppression was first recognized as critical and nonredundant in protecting normal tissues from inflammatory damage and autoimmunity. However, this immunosuppressive mechanism can be highjacked by bacteria and tu...
journal_title:Cancer immunology research
pub_type: 杂志文章,评审
doi:10.1158/2326-6066.CIR-14-0075
更新日期:2014-07-01 00:00:00
abstract::The FDA-AACR Oncology Dose-Finding Workshop, Part 3, was held in Washington, DC, on July 20, 2017, as a continuation of the previous two collaborative dose-finding and optimization workshops presented by the FDA and AACR. This year's workshop focused on combination therapy with immune-oncology agents and best practice...
journal_title:Cancer immunology research
pub_type:
doi:10.1158/2326-6066.CIR-17-0590
更新日期:2017-12-01 00:00:00
abstract::We conducted in vitro studies and a clinical trial for patients with squamous cell carcinoma of the head and neck (SCCHN) to study the relationship between FcγRIIIa polymorphisms and antibody-dependent cellular cytotoxicity (ADCC). In vitro, FcγRIIIa genotype was correlated with ADCC and innate cytotoxicity using natu...
journal_title:Cancer immunology research
pub_type: 杂志文章,多中心研究
doi:10.1158/2326-6066.CIR-14-0188
更新日期:2015-05-01 00:00:00
abstract::Colorectal cancer consists of a small number of cancer stem cells (CSC) and many non-CSCs. Although rare in number, CSCs are a target for cancer therapy, because they survive conventional chemo- and radiotherapies and perpetuate tumor formation in vivo In this study, we conducted an HLA ligandome analysis to survey HL...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-17-0518
更新日期:2018-03-01 00:00:00
abstract::Pancreatic cancer is a devastating disease that is largely refractory to currently available treatment strategies. Therapeutic resistance is partially attributed to the dense stromal reaction of pancreatic ductal adenocarcinoma tumors that includes a pervasive infiltration of immunosuppressive (M2) macrophages. Nab-pa...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-16-0125
更新日期:2017-03-01 00:00:00
abstract::Advanced and metastatic squamous cell carcinomas (SCC) are common and difficult-to-treat malignancies. We assessed 75 immunotherapy-treated patients with SCC from a clinically annotated database of 2,651 patients, as well as 9,407 patients from a deidentified database for molecular features that might influence checkp...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-18-0716
更新日期:2019-06-01 00:00:00
abstract::Ligand-receptor complexes play a central role in mediating a range of processes in immunology and cancer biology. The ability to directly quantify the fraction of receptors occupied by a ligand in a given biospecimen, as opposed to assessing the concentration of ligand and receptor separately, could provide an additio...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-18-0821
更新日期:2019-09-01 00:00:00
abstract::Antibody-drug conjugates (ADC) are emerging as powerful treatment strategies with outstanding target-specificity and high therapeutic activity in patients with cancer. Brentuximab vedotin represents a first-in-class ADC directed against CD30(+) malignancies. We hypothesized that its sustained clinical responses could ...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-13-0198
更新日期:2014-08-01 00:00:00
abstract::The prognosis is very dismal for patients with relapsed CD20(+) B-cell non-Hodgkin lymphoma (B-NHL). Facilitating the development of alternative novel therapeutic strategies is required to improve outcomes in patients with recurrent/refractory CD20(+) B-NHL. In this study, we investigated functional activities of anti...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-14-0114
更新日期:2015-04-01 00:00:00
abstract::The goal of this study was to characterize the molecular mechanisms underlying cetuximab-mediated upregulation of HLA class I antigen-processing machinery components in head and neck cancer (HNC) cells and to determine the clinical significance of these changes in cetuximab-treated HNC patients. Flow cytometry, signal...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-15-0053
更新日期:2015-08-01 00:00:00
abstract::Human papillomavirus type 16 (HPV16) is the etiologic factor for cervical cancer and a subset of oropharyngeal cancers. Although several prophylactic HPV vaccines are available, no effective therapeutic strategies to control active HPV diseases exist. Tumor implantation models are traditionally used to study HPV-assoc...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-16-0358
更新日期:2018-03-01 00:00:00
abstract::The presence and activity of CD8+ T cells within the tumor microenvironment are essential for the control of tumor growth. Utilizing B16-F10 melanoma tumors that express altered peptide ligands of chicken ovalbumin, OVA257-264, we measured high- and low-affinity OVA-specific responses following adoptive transfer of OT...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-19-0690
更新日期:2020-04-01 00:00:00
abstract::Despite HER2-targeted therapies improving the outcome of HER2+ breast cancer, many patients experience resistance and metastatic progression. Cancer stem cells (CSC) play a role in this resistance and progression, thus combining HER2 targeting with CSC inhibition could improve the management of HER2+ breast cancer. Th...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-20-0082
更新日期:2020-08-01 00:00:00
abstract::Tertiary lymphoid structures (TLS) are ectopic lymphoid aggregates that phenotypically resemble conventional secondary lymphoid organs and are commonly found at sites of chronic inflammation. They are also found in a wide variety of primary and metastatic human tumors. The presence of tumor-associated TLS (TA-TLS) is ...
journal_title:Cancer immunology research
pub_type: 杂志文章,评审
doi:10.1158/2326-6066.CIR-20-0432
更新日期:2020-11-01 00:00:00
abstract::Pancreatic ductal adenocarcinoma (PDA) is an aggressive malignancy characterized by a paucity of tumor-proximal CD8+ T cells and resistance to immunotherapeutic interventions. Cancer-associated mechanisms that elicit CD8+ T-cell exclusion and resistance to immunotherapy are not well-known. Here, using a Kras- and p53-...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-19-0349
更新日期:2020-03-01 00:00:00
abstract::The antibodies produced initially in response to most antigens are high molecular weight (MW) immunoglobulins (IgM) with low affinity for the antigen, while the antibodies produced later are lower MW classes (e.g., IgG and IgA) with, on average, orders of magnitude higher affinity for that antigen. These changes, ofte...
journal_title:Cancer immunology research
pub_type: 杂志文章,评审
doi:10.1158/2326-6066.CIR-14-0029
更新日期:2014-05-01 00:00:00
abstract::Natural killer cell (NKc)-based therapies offer promising outcomes in patients with tumors, but they could improve with appropriate selection of donors and optimization of methods to expand NKcs in vitro Education through licensing interactions of inhibitory killer cell immunoglobulin-like receptors (iKIR) and NKG2A w...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-18-0022
更新日期:2018-12-01 00:00:00
abstract::Efficacious antitumor immune responses must overcome multiple suppressive mechanisms in the tumor microenvironment to control cancer progression. In this study, we demonstrate that dual targeting of suppressive myeloid populations by inhibiting CSF-1/CSF-1R signaling and activation of antigen-presenting cells with ago...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-17-0258
更新日期:2017-12-01 00:00:00
abstract::Immunotherapy with monoclonal antibodies targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4) or programmed cell death 1 (PD-1) has improved the survival of patients with metastatic melanoma. These agents carry a certain risk of adverse immune-related events. We present a patient with widely metastatic melanoma who was...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-15-0141
更新日期:2015-12-01 00:00:00
abstract::Vaccinia virus (VACV) is a double-stranded DNA virus that devotes a large portion of its 200 kbp genome to suppressing and manipulating the immune response of its host. Here, we investigated how targeted removal of immunomodulatory genes from the VACV genome impacted immune cells in the tumor microenvironment with the...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-19-0703
更新日期:2020-05-01 00:00:00
abstract::Macroenvironmental factors, including a patient's physical and social environment, play a role in cancer risk and progression. Our previous studies show that living in an enriched environment (EE) providing complex stimuli confers an anticancer phenotype in mice mediated, in part by a specific neuroendocrine axis, wit...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-15-0297
更新日期:2016-06-01 00:00:00
abstract::Monoclonal antibodies (mAb) can modulate cancer cell signal transduction and recruit antitumor immune effector mechanisms-including antibody-dependent cellular cytotoxicity (ADCC). Although several clinically effective antibodies can promote ADCC, therapeutic resistance is common. We hypothesized that oncogenic signal...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-14-0083
更新日期:2014-12-01 00:00:00
abstract::Innate lymphoid cells (ILC) are responsible for mucosal tissue homeostasis and are involved in the progression and suppression of several types of cancer. However, the effects of ILCs on colorectal cancer are poorly understood. We characterized human ILCs in normal colon and colorectal cancer tissue, investigating the...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-19-0775
更新日期:2020-06-01 00:00:00
abstract::Multiple myeloma is characterized by the clonal expansion of malignant plasma cells in the bone marrow. But the phenotypic diversity and the contribution of less predominant B-lineage clones to the biology of this disease have been controversial. Here, we asked whether cells bearing the dominant multiple myeloma immun...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-17-0012
更新日期:2017-09-01 00:00:00
abstract::Immunotherapies targeting T lymphocytes are revolutionizing cancer therapy but only benefit a subset of patients, especially in colorectal cancer. Thus, additional insight into the tumor microenvironment (TME) is required. Eosinophils are bone marrow-derived cells that have been largely studied in the context of aller...
journal_title:Cancer immunology research
pub_type: 杂志文章
doi:10.1158/2326-6066.CIR-18-0494
更新日期:2019-03-01 00:00:00